Know Cancer

forgot password

Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma

Phase 1
18 Years
Open (Enrolling)
Lymphoma, Small Intestine Cancer

Thank you

Trial Information

Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma



- To assess dose-limiting and nonhematologic toxicity of prolonged administration of
vorinostat (SAHA) when administered after autologous peripheral blood stem cell
transplantation in patients with high-risk lymphoma.


- To determine, preliminarily, clinical activity by assessing the overall survival and
progression-free survival.

- To evaluate the effect of vorinostat on immune reconstruction and acetylation.

- To obtain pilot data regarding an association of vorinostat with patient quality of
life and inflammatory cytokine production of peripheral blood mononuclear cells.

OUTLINE: This is a dose-escalation study of vorinostat (SAHA).

Approximately 60 days after autologous hematopoietic stem cell transplantation (HSCT),
patients receive oral vorinostat once daily on days 1-21. Treatment repeats every 28 days
for up to 11 courses in the absence of unacceptable toxicity or disease progression.

Blood and bone marrow samples are collected periodically for laboratory correlative studies
comprising immune reconstitution assays, regulatory T-cell expansion analysis, H3 and H4
acetylation by immunohistochemistry, cytokine bead array to quantify interleukin (IL)-2,
IL-4, IL-5, IL-6, IL-10, tumor necrosis factor alpha and interferon gamma. Quality of life
correlative studies are measured by questionnaires periodically.

After completion of study treatment, patients are followed for at least 30 days.

Inclusion Criteria


- Must have received a BEAM (cytarabine, etoposide, melphalan, carmustine)-conditioned
autologous stem cell transplantation for any of the following high-risk lymphomas:

- Diffuse large B-cell lymphoma as defined by:

- Induction failure but with response to salvage therapy

- Relapse less than one year after completion of induction therapy

- Elevated lactate dehydrogenase (LDH) at relapse

- Stage III/IV disease at relapse

- Positive PET scan after induction or salvage therapy

- Age ≤ 75 and ≥ 60 years

- Follicular lymphoma as defined by:

- Progressive disease after two or more prior regimens

- Transformed to aggressive lymphoma but still chemotherapy sensitive

- Not felt to be a good candidate for an allogeneic transplantation

- Hodgkin lymphoma as defined by:

- Primary refractory disease

- Relapse less than one year after completion of induction therapy

- Relapse with PET-positive disease after salvage therapy

- Relapsed refractory and not felt to be a good candidate for an allogeneic

- Mantle cell lymphoma

- Chemotherapy-sensitive disease after induction therapy

- Chemotherapy-sensitive relapsed disease and not felt to be a good candidate
for an allogeneic transplantation

- T-cell non-Hodgkin lymphoma (NHL)

- Peripheral T-cell lymphoma not otherwise specified and one or more of the
following at diagnosis:

- High LDH

- Marrow involvement

- Age > 60 years

- Low platelet count

- Relapsed chemotherapy-sensitive disease

- Angioimmunoblastic lymphadenopathy with dysproteinemia

- Anaplastic lymphoma kinase-negative anaplastic NHL

- Enteropathy-associated T-cell NHL

- Natural killer (NK)/T-cell NHL and stage III/IV disease at diagnosis

- NK blastic NHL


- ECOG/WHO performance status 0-2

- ANC ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Total bilirubin ≤ 1.5 mg/dL

- AST/ALT ≤ 2 x upper limit of normal (ULN)

- Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 50 mL/min

- No severe or uncontrolled systemic illness

- Patients must be able to swallow capsules

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use at least two adequate barrier methods of contraception
during study and for 90 days after completion of study therapy

- No other malignancy within the past 5 years other than nonmelanoma skin cancer,
carcinoma in situ of the cervix, or a malignancy considered by their physician to be
at less than 30% risk of relapse

- No congenital long QT syndrome

- No significant history of uncontrolled cardiac disease (i.e., uncontrolled
hypertension, unstable angina, myocardial infarction within the past 6 months, or
uncontrolled congestive heart failure)

- No active bacterial, fungal, or viral infection

- No known HIV infection

- No active hepatitis B and/or hepatitis C infection

- No other medical condition, including mental illness or substance abuse, deemed by
the Investigator(s) to interfere with a patient's ability to sign informed consent,
cooperate and participate in the study, or interfere with the interpretation of the


- Recovered from the majority of the toxicities from the autologous transplantation
(must have returned to their pretransplant baseline or have no greater than grade I
extramedullary toxicity [CTCAE 3.0])

- No prior treatment with a histone deacetylase (HDAC) inhibitor (e.g., depsipeptide,
MS-275, LAQ-824, belinostat, valproic acid)

- More than 4 weeks since prior and no concurrent class Ia, Ib, or Ic antiarrhythmic

- No other concurrent antineoplastic chemotherapy or biologic therapy

- No concurrent radiotherapy, unless for local control of bone pain

- Irradiated area for pain management should be as small as possible and lesions
within the irradiated field cannot be used for response

- No concurrent use of complementary or alternative medicines that would confound the
interpretation of toxicities and antitumor activity of vorinostat (SAHA)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of vorinostat (SAHA) after autologous stem cell transplantation

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Craig C. Hofmeister, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

Related Keywords:

  • Lymphoma
  • Small Intestine Cancer
  • recurrent adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent mantle cell lymphoma
  • adult nasal type extranodal NK/T-cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • stage III adult T-cell leukemia/lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • small intestine lymphoma
  • anaplastic large cell lymphoma
  • Lymphoma
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms



Ohio State University Medical Center Columbus, Ohio  43210